This project evaluates a wide variety of factors which contribute to the urinary excretion of 3-methoxy-4-hydroxphenylglycol (MHPG), the norepinephrine metabolite thought best to reflect brain turnover. Major findings are as follows: (1) 24-hour urinary MHPG excretion is low in depression and high in mania but can not be used to indicate mood change; (2) Depressed patients vs. volunteers show an altered circadian rhythm in MHPG with a maximum difference in the late evening; (3) MHPG changes induced by diet and physical activity are confirmed to be restricted to depressed patients, suggesting defective "buffering" of norepinephrine turnover; (4) urinary free cortisol (UFC), which is controlled by ACTH secretion, is found to have an inverse relationship to urinary MHPG in depressed patients--since ACTH secretion is inhibited by norepinephrine, the findings support the hypothesis that urinary MHPG and UFC are indices of central norepinephrine turnover. BIBLIOGRAPHIC REFERENCES: Beckmann, H., van Kammen, D.P., Goodwin, F.K. and Murphy, D.L.: Urinary Excretion of 3-Methoxy-4-hydroxyphenylglycol in Depressed Patients: Modifications by Amphetamine and Lithium. Biol. Psychiat. 11:377-387, 1976.